COVID-19 Symptoms and Duration of Rapid Antigen Test Positivity at a Community Testing and Surveillance Site During Pre-Delta, Delta, and Omicron BA.1 Periods.

Importance: Characterizing the clinical symptoms and evolution of community-based SARS-CoV-2 infections may inform health practitioners and public health officials in a rapidly changing landscape of population immunity and viral variants. Objectives: To compare COVID-19 symptoms among people testing positive with a rapid antigen test (RAT) during the Omicron BA.1 variant period (December 1, 2021, to January 30, 2022) with the pre-Delta (January 10 to May 31, 2021) and Delta (June 1 to November 30, 2021) variant periods and to assess the duration of RAT positivity during the Omicron BA.1 surge. Design, Setting, and Participants: This cross-sectional study was conducted from January 10, 2021, to January 31, 2022, at a walk-up community COVID-19 testing site in San Francisco, California. Participants included children and adults seeking COVID-19 testing with an RAT, regardless of age, vaccine status, or symptoms. Main Outcomes and Measures: Fisher exact tests or χ2 tests were used to compare COVID-19 symptoms during the Omicron BA.1 period with the pre-Delta and Delta periods for vaccination status and age group. Among people returning for repeated testing during the Omicron period, the proportion with a positive RAT between 4 and 14 days from symptom onset or since first positive test if asymptomatic was estimated. Results: Among 63 277 persons tested (median [IQR] age, 32 [21-44] years, with 12.0% younger than 12 years; 52.0% women; and 68.5% Latinx), a total of 18 301 people (28.9%) reported symptoms, of whom 4565 (24.9%) tested positive for COVID-19. During the Omicron BA.1 period, 3032 of 7283 symptomatic participants (41.6%) tested positive, and the numbers of these reporting cough and sore throat were higher than during pre-Delta and Delta periods (cough: 2044 [67.4%] vs 546 [51.3%] of 1065 participants, P < .001 for pre-Delta, and 281 [60.0%] of 468 participants, P = .002, for Delta; sore throat: 1316 [43.4%] vs 315 [29.6%] of 1065 participants, P < .001 for pre-Delta, and 136 [29.1%] of 468 participants, P < .001, for Delta). Compared with the 1065 patients with positive test results in the pre-Delta period, congestion among the 3032 with positive results during the Omicron BA.1 period was more common (1177 [38.8%] vs 294 [27.6%] participants, P < .001), and loss of taste or smell (160 [5.3%] vs 183 [17.2%] participants, P < .001) and fever (921 [30.4%] vs 369 [34.7%] participants, P = .01) were less common. In addition, during the Omicron BA.1 period, fever was less common among the people with positive test results who had received a vaccine booster compared with those with positive test results who were unvaccinated (97 [22.5%] of 432 vs 42 [36.2%] of 116 participants, P = .003), and fever and myalgia were less common among participants who had received a booster compared with those with positive results who had received only a primary series (fever: 97 [22.5%] of 432 vs 559 [32.8%] of 1705 participants, P < .001; myalgia: 115 [26.6%] of 432 vs 580 [34.0%] of 1705 participants, P = .003). During the Omicron BA.1 period, 5 days after symptom onset, 507 of 1613 people (31.1%) with COVID-19 stated that their symptoms were similar, and 95 people (5.9%) reported worsening symptoms. Among people testing positive, 80.2% of participants who were symptomatic and retested remained positive 5 days after symptom onset. Conclusions and Relevance: In this cross-sectional study, COVID-19 upper respiratory tract symptoms were more commonly reported during the Omicron BA.1 period than during the pre-Delta and Delta periods, with differences by vaccination status. Rapid antigen test positivity remained high 5 days after symptom onset, supporting guidelines requiring a negative test to inform the length of the isolation period.

Brief Report: Heterogeneous Preferences for Care Engagement Among People With HIV Experiencing Homelessness or Unstable Housing During the COVID-19 Pandemic.

BACKGROUND/SETTING: In San Francisco, HIV viral suppression is 71% among housed individuals but only 20% among unhoused individuals. We conducted a discrete choice experiment at a San Francisco public HIV clinic to evaluate care preferences among people living with HIV (PLH) experiencing homelessness/unstable housing during the COVID-19 pandemic. METHODS: From July to November 2020, we conducted a discrete choice experiment among PLH experiencing homelessness/unstable housing who accessed care through (1) an incentivized, drop-in program (POP-UP) or (2) traditional primary care. We investigated 5 program features: single provider vs team of providers; visit incentives ($0, $10, and $20); location (current site vs current + additional site); drop-in vs scheduled visits; in-person only vs optional telehealth visits; and navigator assistance. We estimated relative preferences using mixed-effects logistic regression and conducted latent class analysis to evaluate preference heterogeneity. RESULTS: We enrolled 115 PLH experiencing homelessness/unstable housing, 40% of whom lived outdoors. The strongest preferences were for the same provider (ß = 0.94, 95% CI: 0.48 to 1.41), visit incentives (ß = 0.56 per $5; 95% CI: 0.47 to 0.66), and drop-in visits (ß = 0.47, 95% CI: 0.12 to 0.82). Telehealth was not preferred. Latent class analysis revealed 2 distinct groups: 78 (68%) preferred a flexible care model, whereas 37 (32%) preferred a single provider. CONCLUSIONS: We identified heterogeneous care preferences among PLH experiencing homelessness/unstable housing during the COVID-19 pandemic, with two-thirds preferring greater flexibility and one-third preferring provider continuity. Telehealth was not preferred, even with navigator facilitation. Including patient choice in service delivery design can improve care engagement, particularly for marginalized populations, and is an essential tool for ending the HIV epidemic.

Integrating Rapid Diabetes Screening Into a Latinx Focused Community-Based Low-Barrier COVID-19 Testing Program.

Importance: Community-based COVID-19 testing and vaccination programs play a crucial role in mitigating racial and ethnic disparities in COVID-19 service delivery. They also represent a platform that can be leveraged to expand access to testing for chronic diseases, including diabetes, that disproportionately affect the Latinx community and other marginalized communities. Objective: To evaluate outcomes associated with a diabetes testing strategy designed to reach low-income Latinx persons by leveraging COVID-19 testing infrastructure and community trust developed during the COVID-19 pandemic. Design, Setting, and Participants: This health care improvement study was conducted from August 1 to October 5, 2021, at an outdoor, community-based COVID-19 testing site at a transport hub in the Mission Neighborhood in San Francisco, California. Because the program was designed to expand access to diabetes screening to the local community, all individuals presenting for on-site testing were eligible. Data were analyzed in November 2021. Interventions: Integration of rapid, point-of-care hemoglobin A1c screening as a testing option in an existing low-barrier COVID-19 testing program. Main Outcomes and Measures: Evaluation was guided by the Reach, Effectiveness, Adoption, Implementation and Maintenance (RE-AIM) framework and utilized programmatic data and structured surveys among clients and staff. Results: Of 6631 individuals tested (median [IQR] age 39.3 [29.7-51.3] years; 3417 [52.3%] female, 4348 [65.6%] Latinx), 923 (13.9%) underwent hemoglobin A1c testing with or without COVID-19 testing and 5708 (86.1%) underwent COVID-19 testing only. Individuals tested for diabetes were more likely to be Latinx (763 of 923 individuals [82.7%] who underwent testing were Latinx vs 3585 of 5708 [62.8%] not undergoing testing), have an annual household income of less than $50 000 (450 individuals [81.2%] vs 2409 individuals [66.0%]), and not have health insurance (381 individuals [47.2%] vs 1858 individuals [39.9%]), and 206 (48.0%) had never tested for diabetes before. Overall, 313 (33.9%) and 113 (12.2%) individuals had prediabetes and diabetes, respectively; only 141 of 354 of these individuals (39.8%) had a primary care clinician whom they had seen in the prior 12 months, which was lower among Latinx individuals (113 of 307 individuals [36.8%] vs 28 of 47 [59.6%]). Acceptability of the rapid testing program was high-98% were satisfied with their visit and 96% said they would return for future services; key factors underpinning acceptability included friendly staff, efficiency, and a convenient location. Conclusions and Relevance: In this health care improvement study conducted within an existing community-based COVID-19 testing program, integrating rapid testing for diabetes was feasible, reached low-income Latinx individuals, and identified many persons with prediabetes and diabetes, most of whom lacked access to services in formal health care settings. Leveraging pandemic-related public health responses represents an important opportunity for engaging socioeconomically disadvantaged populations into care for diabetes.

Tuberculosis screening among ambulatory people living with HIV: a systematic review and individual participant data meta-analysis.

BACKGROUND: The WHO-recommended tuberculosis screening and diagnostic algorithm in ambulatory people living with HIV is a four-symptom screen (known as the WHO-recommended four symptom screen [W4SS]) followed by a WHO-recommended molecular rapid diagnostic test (eg Xpert MTB/RIF [hereafter referred to as Xpert]) if W4SS is positive. To inform updated WHO guidelines, we aimed to assess the diagnostic accuracy of alternative screening tests and strategies for tuberculosis in this population. METHODS: In this systematic review and individual participant data meta-analysis, we updated a search of PubMed (MEDLINE), Embase, the Cochrane Library, and conference abstracts for publications from Jan 1, 2011, to March 12, 2018, done in a previous systematic review to include the period up to Aug 2, 2019. We screened the reference lists of identified pieces and contacted experts in the field. We included prospective cross-sectional, observational studies and randomised trials among adult and adolescent (age ≥10 years) ambulatory people living with HIV, irrespective of signs and symptoms of tuberculosis. We extracted study-level data using a standardised data extraction form, and we requested individual participant data from study authors. We aimed to compare the W4SS with alternative screening tests and strategies and the WHO-recommended algorithm (ie, W4SS followed by Xpert) with Xpert for all in terms of diagnostic accuracy (sensitivity and specificity), overall and in key subgroups (eg, by antiretroviral therapy [ART] status). The reference standard was culture. This study is registered with PROSPERO, CRD42020155895. FINDINGS: We identified 25 studies, and obtained data from 22 studies (including 15 666 participants; 4347 [27·7%] of 15 663 participants with data were on ART). W4SS sensitivity was 82% (95% CI 72-89) and specificity was 42% (29-57). C-reactive protein (≥10 mg/L) had similar sensitivity to (77% [61-88]), but higher specificity (74% [61-83]; n=3571) than, W4SS. Cough (lasting ≥2 weeks), haemoglobin (<10 g/dL), body-mass index (<18·5 kg/m2), and lymphadenopathy had high specificities (80-90%) but low sensitivities (29-43%). The WHO-recommended algorithm had a sensitivity of 58% (50-66) and a specificity of 99% (98-100); Xpert for all had a sensitivity of 68% (57-76) and a specificity of 99% (98-99). In the one study that assessed both, the sensitivity of sputum Xpert Ultra was higher than sputum Xpert (73% [62-81] vs 57% [47-67]) and specificities were similar (98% [96-98] vs 99% [98-100]). Among outpatients on ART (4309 [99·1%] of 4347 people on ART), W4SS sensitivity was 53% (35-71) and specificity was 71% (51-85). In this population, a parallel strategy (two tests done at the same time) of W4SS with any chest x-ray abnormality had higher sensitivity (89% [70-97]) and lower specificity (33% [17-54]; n=2670) than W4SS alone; at a tuberculosis prevalence of 5%, this strategy would require 379 more rapid diagnostic tests per 1000 people living with HIV than W4SS but detect 18 more tuberculosis cases. Among outpatients not on ART (11 160 [71·8%] of 15 541 outpatients), W4SS sensitivity was 85% (76-91) and specificity was 37% (25-51). C-reactive protein (≥10 mg/L) alone had a similar sensitivity to (83% [79-86]), but higher specificity (67% [60-73]; n=3187) than, W4SS and a sequential strategy (both test positive) of W4SS then C-reactive protein (≥5 mg/L) had a similar sensitivity to (84% [75-90]), but higher specificity than (64% [57-71]; n=3187), W4SS alone; at 10% tuberculosis prevalence, these strategies would require 272 and 244 fewer rapid diagnostic tests per 1000 people living with HIV than W4SS but miss two and one more tuberculosis cases, respectively. INTERPRETATION: C-reactive protein reduces the need for further rapid diagnostic tests without compromising sensitivity and has been included in the updated WHO tuberculosis screening guidelines. However, C-reactive protein data were scarce for outpatients on ART, necessitating future research regarding the utility of C-reactive protein in this group. Chest x-ray can be useful in outpatients on ART when combined with W4SS. The WHO-recommended algorithm has suboptimal sensitivity; Xpert for all offers slight sensitivity gains and would have major resource implications. FUNDING: World Health Organization.

Interrupted time-series analysis of active case-finding for tuberculosis during the COVID-19 pandemic, Zambia.

Objective: To evaluate the impact of the coronavirus disease 2019 (COVID-19) pandemic and the subsequent implementation of tuberculosis response measures on tuberculosis notifications in Zambia. Methods: We used an interrupted time-series design to compare monthly tuberculosis notifications in Zambia before the pandemic (January 2019 to February 2020), after implementation of national pandemic mitigation measures (April 2020 to June 2020) and after response measures to improve tuberculosis detection (August 2020 to September 2021). The tuberculosis response included enhanced data surveillance, facility-based active case-finding and activities to generate demand for services. We used nationally aggregated, facility-level tuberculosis notification data for the analysis. Findings: Pre-pandemic tuberculosis case notifications rose steadily from 2890 in January 2019 to 3337 in February 2020. After the start of the pandemic and mitigation measures, there was a -22% (95% confidence interval, CI: -24 to -19) immediate decline in notifications in April 2020. Larger immediate declines in notifications were seen among human immunodeficiency virus (HIV)-positive compared with HIV-negative individuals (-36%; 95% CI: -38 to -35; versus -12%; 95% CI: -17 to -6). Following roll-out of tuberculosis response measures in July 2020, notifications immediately increased by 45% (95% CI: 38 to 51) nationally and across all subgroups and provinces. The trend in notifications remained stable through September 2021, with similar numbers to the predicted number had the pandemic not occurred. Conclusion: Implementation of a coordinated public health response including active tuberculosis case-finding was associated with reversal of the adverse impact of the pandemic and mitigation measures. The gains were sustained throughout subsequent waves of the pandemic.

Interrupted time-series analysis of active case-finding for tuberculosis during the COVID-19 pandemic, Zambia Analyse d'une série chronologique interrompue de dépistage actif des cas de tuberculose durant la pandémie de COVID-19 en Zambie Análisis de series temporales interrumpidas sobre la búsqueda activa de casos de tuberculosis durante la pandemia de la COVID-19 en Zambia .تحليل السلاسل الزمنية المتقطع لاكتشاف الحالات النشطة لمرض السل أثناء جائحة كوفيد 19، زامبيا 赞比亚新型冠状病毒肺炎疫情期间结核病主动病例发现的中断时间序列分析 Анализ прерванных временных рядов для активного выявления случаев заболевания туберкулезом во время пандемии COVID-19, Замбия

Objective To evaluate the impact of the coronavirus disease 2019 (COVID-19) pandemic and the subsequent implementation of tuberculosis response measures on tuberculosis notifications in Zambia. Methods We used an interrupted time-series design to compare monthly tuberculosis notifications in Zambia before the pandemic (January 2019 to February 2020), after implementation of national pandemic mitigation measures (April 2020 to June 2020) and after response measures to improve tuberculosis detection (August 2020 to September 2021). The tuberculosis response included enhanced data surveillance, facility-based active case-finding and activities to generate demand for services. We used nationally aggregated, facility-level tuberculosis notification data for the analysis. Findings Pre-pandemic tuberculosis case notifications rose steadily from 2890 in January 2019 to 3337 in February 2020. After the start of the pandemic and mitigation measures, there was a −22% (95% confidence interval, CI: −24 to −19) immediate decline in notifications in April 2020. Larger immediate declines in notifications were seen among human immunodeficiency virus (HIV)-positive compared with HIV-negative individuals (−36%;95% CI: −38 to −35;versus −12%;95% CI: −17 to −6). Following roll-out of tuberculosis response measures in July 2020, notifications immediately increased by 45% (95% CI: 38 to 51) nationally and across all subgroups and provinces. The trend in notifications remained stable through September 2021, with similar numbers to the predicted number had the pandemic not occurred. Conclusion Implementation of a coordinated public health response including active tuberculosis case-finding was associated with reversal of the adverse impact of the pandemic and mitigation measures. The gains were sustained throughout subsequent waves of the pandemic.

Addressing health disparities through implementation science-a need to integrate an equity lens from the outset.

There is increasing attention being given to opportunities and approaches to advance health equity using implementation science. To reduce disparities in health, it is crucial that an equity lens is integrated from the earliest stages of the implementation process. In this paper, we outline four key pre-implementation steps and associated questions for implementation researchers to consider that may help guide selection and design of interventions and associated implementation strategies that are most likely to reach and be effective in reducing health disparities among vulnerable persons and communities.

A multi-component, community-based strategy to facilitate COVID-19 vaccine uptake among Latinx populations: From theory to practice.

BACKGROUND: COVID-19 vaccine coverage in the Latinx community depends on delivery systems that overcome barriers such as institutional distrust, misinformation, and access to care. We hypothesized that a community-centered vaccination strategy that included mobilization, vaccination, and "activation" components could successfully reach an underserved Latinx population, utilizing its social networks to boost vaccination coverage. METHODS: Our community-academic-public health partnership, "Unidos en Salud," utilized a theory-informed approach to design our "Motivate, Vaccinate, and Activate" COVID-19 vaccination strategy. Our strategy's design was guided by the PRECEDE Model and sought to address and overcome predisposing, enabling, and reinforcing barriers to COVID-19 vaccination faced by Latinx individuals in San Francisco. We evaluated our prototype outdoor, "neighborhood" vaccination program located in a central commercial and transport hub in the Mission District in San Francisco, using the Reach, Effectiveness, Adoption, Implementation and Maintenance (RE-AIM) framework during a 16-week period from February 1, 2021 to May 19, 2021. Programmatic data, city-wide COVID-19 surveillance data, and a survey conducted between May 2, 2021 and May 19, 2021 among 997 vaccinated clients ≥16 years old were used in the evaluation. RESULTS: There were 20,792 COVID-19 vaccinations administered at the neighborhood site during the 16-week evaluation period. Vaccine recipients had a median age of 43 (IQR 32-56) years, 53.9% were male and 70.5% were Latinx, 14.1% white, 7.7% Asian, 2.4% Black, and 5.3% other. Latinx vaccinated clients were substantially more likely than non-Latinx clients to have an annual household income of less than $50,000 a year (76.1% vs. 33.5%), be a first-generation immigrant (60.2% vs. 30.1%), not have health insurance (47.3% vs. 16.0%), and not have access to primary care provider (62.4% vs. 36.2%). The most frequently reported reasons for choosing vaccination at the site were its neighborhood location (28.6%), easy and convenient scheduling (26.9%) and recommendation by someone they trusted (18.1%); approximately 99% reported having an overall positive experience, regardless of ethnicity. Notably, 58.3% of clients reported that they were able to get vaccinated earlier because of the neighborhood vaccination site, 98.4% of clients completed both vaccine doses, and 90.7% said that they were more likely to recommend COVID-19 vaccination to family and friends after their experience; these findings did not substantially differ according to ethnicity. There were 40.3% of vaccinated clients who said they still knew at least one unvaccinated person (64.6% knew ≥3). Among clients who received both vaccine doses (n = 729), 91.0% said that after their vaccination experience, they had personally reached out to at least one unvaccinated person they knew (61.6% reached out to ≥3) to recommend getting vaccinated; 83.0% of clients reported that one or more friends, and/or family members got vaccinated as a result of their outreach, including 18.9% who reported 6 or more persons got vaccinated as a result of their influence. CONCLUSIONS: A multi-component, "Motivate, Vaccinate, and Activate" community-based strategy addressing barriers to COVID-19 vaccination for the Latinx population reached the intended population, and vaccinated individuals served as ambassadors to recruit other friends and family members to get vaccinated.

Community Transmission of Severe Acute Respiratory Syndrome Coronavirus 2 Disproportionately Affects the Latinx Population During Shelter-in-Place in San Francisco.

BACKGROUND: There is an urgent need to understand the dynamics and risk factors driving ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission during shelter-in-place mandates. METHODS: We offered SARS-CoV-2 reverse-transcription polymerase chain reaction (PCR) and antibody (Abbott ARCHITECT IgG) testing, regardless of symptoms, to all residents (aged ≥4 years) and workers in a San Francisco census tract (population: 5174) at outdoor, community-mobilized events over 4 days. We estimated SARS-CoV-2 point prevalence (PCR positive) and cumulative incidence (antibody or PCR positive) in the census tract and evaluated risk factors for recent (PCR positive/antibody negative) vs prior infection (antibody positive/PCR negative). SARS-CoV-2 genome recovery and phylogenetics were used to measure viral strain diversity, establish viral lineages present, and estimate number of introductions. RESULTS: We tested 3953 persons (40% Latinx; 41% White; 9% Asian/Pacific Islander; and 2% Black). Overall, 2.1% (83/3871) tested PCR positive: 95% were Latinx and 52% were asymptomatic when tested; 1.7% of census tract residents and 6.0% of workers (non-census tract residents) were PCR positive. Among 2598 tract residents, estimated point prevalence of PCR positives was 2.3% (95% confidence interval [CI], 1.2%-3.8%): 3.9% (95% CI, 2.0%-6.4%) among Latinx persons vs 0.2% (95% CI, .0-.4%) among non-Latinx persons. Estimated cumulative incidence among residents was 6.1% (95% CI, 4.0%-8.6%). Prior infections were 67% Latinx, 16% White, and 17% other ethnicities. Among recent infections, 96% were Latinx. Risk factors for recent infection were Latinx ethnicity, inability to shelter in place and maintain income, frontline service work, unemployment, and household income <$50 000/year. Five SARS-CoV-2 phylogenetic lineages were detected. CONCLUSIONS: SARS-CoV-2 infections from diverse lineages continued circulating among low-income, Latinx persons unable to work from home and maintain income during San Francisco's shelter-in-place ordinance.

Evaluation of a novel community-based COVID-19 'Test-to-Care' model for low-income populations.

BACKGROUND: After a COVID-19 diagnosis, vulnerable populations face considerable logistical and financial challenges to isolate and quarantine. We developed and evaluated a novel, community-based approach ('Test-to-Care' Model) designed to address these barriers for socioeconomically vulnerable Latinx individuals with newly diagnosed COVID-19 and their households. METHODS: This three-week demonstration project was nested within an epidemiologic surveillance study in a primarily Latinx neighborhood in the Mission district of San Francisco, California. The Test-to-Care model was developed with input from community members and public health leaders. Key components included: (1) provision of COVID-19-related education and information about available community resources, (2) home deliveries of material goods to facilitate safe isolation and quarantine (groceries, personal protective equipment and cleaning supplies), and (3) longitudinal clinical and social support. Newly SARS-CoV-2 PCR-positive participants were eligible to participate. Components of the model were delivered by the Test-to-Care team, which was comprised of healthcare providers and community health workers (CHWs) who provided longitudinal clinic- and community-based support for the duration of the isolation period to augment existing services from the Department of Public Health (DPH). We evaluated the Test-to-Care Model using the Reach, Effectiveness, Adoption, Implementation, Maintenance (RE-AIM) Framework and drew upon multiple data sources including: programmatic data, informal interviews with participants and providers/CHWs and structured surveys among providers/CHWs. RESULTS: Overall, 83 participants in the surveillance study were diagnosed with COVID-19, of whom 95% (79/83) were Latinx and 88% (65/74) had an annual household income <$50,000. Ninety-six percent (80/83) of participants were reached for results disclosure, needs assessment and DPH linkage for contact tracing. Among those who underwent an initial needs assessment, 45% (36/80) were uninsured and 55% (44/80) were not connected to primary care. Sixty-seven percent (56/83) of participants requested community-based CHW support to safely isolate at their current address and 65% (54/83) of all COVID-19 participants received ongoing community support via CHWs for the entire self-isolation period. Participants reported that the intervention was highly acceptable and that their trust increased over time-this resulted in 9 individuals who disclosed a larger number of household members than first reported, and 6 persons who requested temporary relocation to a hotel room for isolation despite initially declining this service; no unintended harms were identified. The Test-to-Care Model was found to be both acceptable and feasible to providers and CHWs. Challenges identified included a low proportion of participants linked to primary care despite support (approximately 10% after one month), and insufficient access to financial support for wage replacement. CONCLUSIONS: The Test-to-Care Model is a feasible and acceptable intervention for supporting self-isolation and quarantine among newly diagnosed COVID-19 patients and their households by directly addressing key barriers faced by socioeconomically vulnerable populations.

Clinical features, diagnostics, and outcomes of patients presenting with acute respiratory illness: A retrospective cohort study of patients with and without COVID-19.

BACKGROUND: Most data on the clinical presentation, diagnostics, and outcomes of patients with COVID-19 have been presented as case series without comparison to patients with other acute respiratory illnesses. METHODS: We examined emergency department patients between February 3 and March 31, 2020 with an acute respiratory illness who were tested for SARS-CoV-2. We determined COVID-19 status by PCR and metagenomic next generation sequencing (mNGS). We compared clinical presentation, diagnostics, treatment, and outcomes. FINDINGS: Among 316 patients, 33 tested positive for SARS-CoV-2; 31 without COVID-19 tested positive for another respiratory virus. Among patients with additional viral testing (27/33), no SARS-CoV-2 co-infections were identified. Compared to those who tested negative, patients with COVID-19 reported longer symptoms duration (median 7d vs. 3d, p < 0.001). Patients with COVID-19 were more often hospitalized (79% vs. 56%, p = 0.014). When hospitalized, patients with COVID-19 had longer hospitalizations (median 10.7d vs. 4.7d, p < 0.001) and more often developed ARDS (23% vs. 3%, p < 0.001). Most comorbidities, medications, symptoms, vital signs, laboratories, treatments, and outcomes did not differ by COVID-19 status. INTERPRETATION: While we found differences in clinical features of COVID-19 compared to other acute respiratory illnesses, there was significant overlap in presentation and comorbidities. Patients with COVID-19 were more likely to be admitted to the hospital, have longer hospitalizations and develop ARDS, and were unlikely to have co-existent viral infections. FUNDING: National Center for Advancing Translational Sciences, National Heart Lung Blood Institute, National Institute of Allergy and Infectious Diseases, Chan Zuckerberg Biohub, Chan Zuckerberg Initiative.